BIOCHEMISTRY OF VITAMIN B12 AND FOLIC ACID COMPOUNDS

维生素 B12 和叶酸化合物的生物化学

• 批准号: 2137976
• 负责人: LARS G LJUNGDAHL
• 金额: $ 22.29万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-12-01 至 1996-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2137976
• 关键词: Clostridium; Raman spectrometry; X ray spectrometry; acetates; acetyl coA; acyl coA dehydrogenases; adenosine triphosphate; anaerobic bacteria; autoradiography; carbon dioxide fixation; circular magnetic dichroism; cytochrome b; electron spin resonance spectroscopy; enzyme activity; enzyme complex; enzyme induction /repression; enzyme linked immunosorbent assay; enzyme structure; ferredoxin; formates; intestines; iron; methanol; microorganism metabolism; nickel; nucleic acid sequence; nutrition related tag; oxidoreductase; protein sequence; radiotracer; rubredoxins; selenium; tetrahydrofolates; tungsten; vitamin B12 compound

The proposed study will be conducted with the acetogenic bacteria Clostridium thermoaceticum, Clostridium thermoautotrophicum and Clostridium formicoaceticum. The important feature of these bacteria is their capacity to synthesize acetate from carbon dioxide. This occurs via a new autotrophic pathway used by a number of anaerobic bacteria present in the intestine of man, many animals and insects. It is a major pathway in anaerobic environments and it is ecologically important. Bacteria using the pathway may in the intestine of man produce 13,000 metric tons of acetate per day from C02 in the total human population. The pathway is known as the acetyl-CoA pathway, because acetyl-CoA is the first 2-carbon compound formed from C02. The initial C02 fixations are catalyzed by formate dehydrogenase and an enzyme with several functions called carbon monoxide dehydrogenase/acetyl-CoA synthtase (CODH). C02 destined to form the methyl group of acetate is first reduced to formate, which is converted to 5-methyltetrahydrofolate and subsequently to methyl-B12. This involves several enzymes that are, tetrahydrofolate- and vitamin B12 dependent. Sequencing and active site studies will be performed. These experiments will give knowledge about enzymes converting 1-carbon compounds, which are needed for DNA, RNA and protein synthesis. C02 to form from the carboxyl group of acetate is first reduced to form carbon monoxide by CODH. This enzyme synthesizes from Co, methyl-B12 and coenzyme A acetyl-CoA. Formate dehydrogenase and CODH contains tungsten, selenium and iron and nickel, zinc and iron, respectively. The role of these elements in the catalytic processes will be studied using isotopes and spectrometric methods such as EPR, XAF, Raman, variable temperature magnetic circular dichroism (VTMCD) . These studies will increase our understanding on how trace elements function in biological reaction catalyzed by enzymes and increase our understanding of a new pathway of medical and ecological importance.

拟开展的研究将与产乙酸菌 热乙酸梭菌、热自养梭菌和 甲酸乙酸梭菌 这些细菌的重要特征是 他们从二氧化碳合成醋酸盐的能力。 发生这种情况 通过一种新的自养途径， 存在于人类、许多动物和昆虫的肠道中。 它是一个主要 在厌氧环境中的途径，它是生态重要。 利用这一途径的细菌在人的肠道中可以产生13000 在总人口中，每天从CO2中产生的乙酸盐的公吨。 该途径被称为乙酰辅酶A途径，因为乙酰辅酶A是 由CO2形成的第一2-碳化合物。 最初的CO2固定是 由甲酸脱氢酶和具有多种功能的酶催化 称为一氧化碳脱氢酶/乙酰辅酶A还原酶（CODH）。C02 预定形成乙酸酯的甲基首先被还原成甲酸酯， 将其转化为5-甲基四氢叶酸， 甲基-B12 这涉及到几种酶，四氢叶酸- 维生素B12依赖 测序和活性位点研究将 执行。 这些实验将提供有关酶的知识 转化DNA、RNA和蛋白质所需的1-碳化合物 合成. 从乙酸酯的羧基形成的CO2首先是 通过CODH还原形成一氧化碳。 这种酶由 Co、甲基-B12和辅酶A乙酰辅酶A。 甲酸脱氢酶和CODH 含有钨、硒、铁和镍、锌、铁， 分别 这些元素在催化过程中的作用将 使用同位素和光谱方法，如EPR，XAF， 拉曼、变温磁性圆二色性（VTMCD）。 这些 研究将增加我们对微量元素如何在人体内发挥作用的理解， 酶催化的生物反应，增加我们对 一条具有医学和生态重要性的新途径。